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Clinical Drug Investigation

, Volume 37, Issue 7, pp 705–707 | Cite as

Long Pulmonary Residence Time and Plasma Half-Life of Tiotropium: Implications for Pharmacokinetic Bioequivalence Studies

  • Ashish SharmaEmail author
  • Benjamin Weber
  • Bernd Meibohm
Letter to the Editor

Dear Editor,

Tiotropium bromide is a once-daily, inhaled long-acting anti-muscarinic bronchodilator that has attained a central role in the management of chronic obstructive pulmonary disease [1]. It is available under the trade name Spiriva® in two formulations manufactured by the drug innovator, Boehringer Ingelheim: an aqueous solution delivered via the Respimat® soft-mist inhaler, and a dry powder (18 µg of tiotropium per capsule) delivered by the HandiHaler® device. Recently, another tiotropium bromide-containing product (13 µg of tiotropium per capsule) administered by the Zonda® dry powder inhaler received regulatory approval in Europe via the decentralized procedure [2]. A clinical trial claiming to demonstrate pharmacokinetic bioequivalence between this product and the Boehringer Ingelheim originator product was recently published in this journal by Algorta et al. [3].

The purpose of this letter is to dispute two claims made by Algorta et al. [3], namely (1) that their...

Notes

Acknowledgements

The authors acknowledge the medical writing support of Dr. Paul Tanswell.

Compliance with Ethical Standards

Funding

This study was funded by Boehringer Ingelheim.

Conflict of interest

Ashish Sharma and Benjamin Weber are employees of Boehringer Ingelheim Pharmaceuticals. Bernd Meibohm has consulted for Boehringer Ingelheim Pharmaceuticals.

References

  1. 1.
    Tashkin DP, Bateman ED, Jones P, Zubek VB, Metzdorf N, Liu D, et al. Consistent improvement in health-related quality of life with tiotropium in patients with chronic obstructive pulmonary disease: novel and conventional responder analyses. Respir Med. 2016;120:91–100. doi: 10.1016/j.rmed.2016.10.002.CrossRefPubMedGoogle Scholar
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    MHRA-UK. Public Assessment Report (PAR). Braltus 10 microgram per delivered dose inhalation powder, hard capsule; Gregal 10 microgram per delivered dose inhalation powder, hard capsule (tiotropium bromide). 2016. Available from: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con723050.pdf. Accessed 19 May 2017.
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    Algorta J, Andrade L, Medina M, Kirkov V, Arsova S, Li F, et al. Pharmacokinetic bioequivalence of two inhaled tiotropium bromide formulations in healthy volunteers. Clin Drug Invest. 2016;36(9):753–62. doi: 10.1007/s40261-016-0441-8.CrossRefGoogle Scholar
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    EMA-CHMP. Questions and answers: positions on specific questions addressed to the Pharmacokinetics Working Party (PKWP). The extent to which plasma levels reflect bioavailability in the lung. Section 17 part 1, p. 44. 2015. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002963.pdf. Accessed 19 May 2017.
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    EMC-UK. Summary of product characteristics: Spiriva 18 microgram inhalation powder, hard capsule. 2015. Available from: http://www.medicines.org.uk/emc/medicine/10039. Accessed 19 May 2017.
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    Weber B, Troconiz IF, Borghardt JM, Staab A, Sharma A. Model-based evaluation of single and multiple dose pharmacokinetics of inhaled tiotropium in healthy volunteers and implications for systemic exposure studies. Respir Drug Deliv Eur. 2015;2:249–54.Google Scholar
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    Sharma A, Weber B, Wein M, Hallmann C, Meibohm B. Essential criteria for pharmacokinetic studies supporting bioequivalence of inhaled tiotropium bromide products. Clin Pharmacol Drug Dev. 2016;5(1):52–6. doi: 10.1002/cpdd.187.CrossRefPubMedGoogle Scholar
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    Weber B, Borghardt JM, Parra-Guillen ZP, Sharma A, Retlich S, Staab A et al. Tiotropium pharmacokinetics and pharmacodynamics: what are drivers for systemic levels and local pulmonary responses? Respir Drug Deliv. 2016;1:45–54.Google Scholar
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    Price D, Sharma A, Cerasoli F. Biochemical properties, pharmacokinetics and pharmacological response of tiotropium in chronic obstructive pulmonary disease patients. Expert Opin Drug Metab Toxicol. 2009;5(4):417–24. doi: 10.1517/17425250902828337.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Translational Medicine and Clinical PharmacologyBoehringer Ingelheim Pharma GmbH & Co. KGBiberach an der RissGermany
  2. 2.Boehringer Ingelheim Pharmaceuticals Inc.RidgefieldUSA
  3. 3.College of PharmacyUniversity of TennesseeMemphisUSA

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